The objective of this proposal is to investigate the mechanism and process of transformation of myeloid cells by the avian acute myeloid leukemia viruses: principally the avian myeloblastosis virus strains AMV BAI-A and E26 and the avain myeloblastosis virus strains MC29 and MH2. The project focuses on the effects of expression of the transformation genes transmitted by these viruses both on the process of differentiation of stem cells into mature granulocytes and macrophages and on the expression of the normal phenotypes in the mature cells. Differentiation will be monitored, morphologically, cytochemically and biochemically using a variety of markers which are specifically expressed in myeloid cells. Additional markers for analysis and separation of the stem cell population will be generated using hybridoma technology. The stem cell population will be derived from 13 day chicken embryo yolk sacs and the mature cells will be obtained by controlled in vitro differentiation of this cell population. The overall process provides mycloid cells at all stages of cell differentiation. Subpopulations of cells will be examined both for their response to transformation and their ability to support virus replication and expression of viral products. The central questions include: (a) What is the mechanism of target cell restriction by these viruses? (b) What controls the differentiation or reversion of the transformed cells? (c) Can transformation block cell differentiation? and (d) Can stem cells be transformed?